Michael Höckel1, Sophia Trott2, Nadja Dornhöfer2, Lars-Christian Horn3, Bettina Hentschel4, Benjamin Wolf2. 1. Department of Gynecology, Women's and Children's Center, University of Leipzig, Leipzig, Germany; Leipzig School of Radical Pelvic Surgery, University of Leipzig, Leipzig, Germany. Electronic address: michael.hoeckel@uniklinik-leipzig.de. 2. Department of Gynecology, Women's and Children's Center, University of Leipzig, Leipzig, Germany. 3. Division of Breast, Gynecological and Perinatal Pathology, Institute of Pathology, University of Leipzig, Leipzig, Germany. 4. Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
Abstract
BACKGROUND: The incidence of vulvar cancer is increasing, but surgical treatment-the current standard of care-often leads to unsatisfactory outcomes, especially in patients with node-positive disease. Preliminary results at our centre showed that locoregional spread of vulvar carcinoma occurs within tissue domains defined by stepwise embryonic and fetal development (ontogenetic cancer fields and associated lymph node regions). We propose that clinical translation of these insights into practice could improve outcomes of surgical treatment of vulvar cancer. METHODS: We did a single-centre prospective trial at the University of Leipzig's Cancer Center. Eligible patients were aged 18 years or older, had ontogenetic stage 1-3b histologically proven primary carcinoma of the vulva, and had not undergone previous surgical or radiotherapy treatment for vulvar cancer or any other major perineal or pelvic disease. In view of staged morphogenesis of the vulva from the cloacal membrane endoderm at Carnegie stage 11 to adulthood, we defined the tissue domains of tumour spread according to the theory of ontogenetic cancer fields. On the basis of ontogenetic staging, patients were treated locally with partial, total, or extended vulvar field resection; regionally with therapeutic inguinopelvic lymph node dissection; and anatomical reconstruction without adjuvant radiotherapy. The primary endpoints were recurrence-free survival, disease-specific survival, and early postoperative complications. Analysis of tumour spread and early postoperative surgical complications was done by intention to treat (ie, all patients were included), whereas outcome analyses were done per protocol. This ongoing trial is registered with the German Clinical Trials Register, number DRKS00013358. FINDINGS: Between March 1, 2009, and June 8, 2017, 97 consecutive patients were included in the study, of whom 94 were treated per protocol with vulvar field resection, therapeutic inguinopelvic lymph node dissection, and anatomical reconstruction without adjuvant radiotherapy. 46 patients had moderate or severe postoperative complications, especially infectious perineal and inguinal wound dehiscence. 3-year recurrence-free survival in all patients was 85·1% (95% CI 76·9-93·3), and 3-year disease-specific survival was 86·0% (78·2-93·8). INTERPRETATION: Our results support the theory of ontogenetic cancer fields for vulvar carcinoma, accord with our previous findings in cervical cancer, and suggest the general applicability of the theory. Application of the concept of cancer field resection could improve outcomes in patients with vulvar carcinoma, but needs to be investigated further in multicentre randomised controlled trials. FUNDING: Leipzig School of Radical Pelvic Surgery and Gynecologic Oncology Research Foundation.
BACKGROUND: The incidence of vulvar cancer is increasing, but surgical treatment-the current standard of care-often leads to unsatisfactory outcomes, especially in patients with node-positive disease. Preliminary results at our centre showed that locoregional spread of vulvar carcinoma occurs within tissue domains defined by stepwise embryonic and fetal development (ontogenetic cancer fields and associated lymph node regions). We propose that clinical translation of these insights into practice could improve outcomes of surgical treatment of vulvar cancer. METHODS: We did a single-centre prospective trial at the University of Leipzig's Cancer Center. Eligible patients were aged 18 years or older, had ontogenetic stage 1-3b histologically proven primary carcinoma of the vulva, and had not undergone previous surgical or radiotherapy treatment for vulvar cancer or any other major perineal or pelvic disease. In view of staged morphogenesis of the vulva from the cloacal membrane endoderm at Carnegie stage 11 to adulthood, we defined the tissue domains of tumour spread according to the theory of ontogenetic cancer fields. On the basis of ontogenetic staging, patients were treated locally with partial, total, or extended vulvar field resection; regionally with therapeutic inguinopelvic lymph node dissection; and anatomical reconstruction without adjuvant radiotherapy. The primary endpoints were recurrence-free survival, disease-specific survival, and early postoperative complications. Analysis of tumour spread and early postoperative surgical complications was done by intention to treat (ie, all patients were included), whereas outcome analyses were done per protocol. This ongoing trial is registered with the German Clinical Trials Register, number DRKS00013358. FINDINGS: Between March 1, 2009, and June 8, 2017, 97 consecutive patients were included in the study, of whom 94 were treated per protocol with vulvar field resection, therapeutic inguinopelvic lymph node dissection, and anatomical reconstruction without adjuvant radiotherapy. 46 patients had moderate or severe postoperative complications, especially infectious perineal and inguinal wound dehiscence. 3-year recurrence-free survival in all patients was 85·1% (95% CI 76·9-93·3), and 3-year disease-specific survival was 86·0% (78·2-93·8). INTERPRETATION: Our results support the theory of ontogenetic cancer fields for vulvar carcinoma, accord with our previous findings in cervical cancer, and suggest the general applicability of the theory. Application of the concept of cancer field resection could improve outcomes in patients with vulvar carcinoma, but needs to be investigated further in multicentre randomised controlled trials. FUNDING: Leipzig School of Radical Pelvic Surgery and Gynecologic Oncology Research Foundation.
Authors: Kim E Kortekaas; Koen K Van de Vijver; Mariëtte I E van Poelgeest; C Blake Gilks; Vincent T H B M Smit; Saimah Arif; Deep Arora; Asma Faruqi; Raji Ganesan; Nicholas R Griffin; Richard Hale; Yelin E Hock; Lars-Christian Horn; W Glenn McCluggage; Pinias Mukonoweshuro; Kay J Park; Brian Rous; Bruce Tanchel; Anne-Sophie Van Rompuy; Gerry van Schalkwyk; Jo Vella; Marco Vergine; Naveena Singh; Tjalling Bosse Journal: Int J Gynecol Pathol Date: 2020-09 Impact factor: 3.326